Expression and role of YAP1 in hepatoblastoma in children

Abstract

Objective To explore the expression of Yes-associated protein1 (YAP1) in pediatric hepatoblastoma, to examine its correlation with patient prognosis and to elucidate the in vitro effects of YAP1 on the proliferation and apoptosis of hepatoblastoma cells. Methods Immunohistochemical staining was utilized for detecting the expressions of YAP1 and β-catenin in 38 cases of hepatoblastoma and adjacent non-tumor tissues. After transfecting YAP1 siRNA into human hepatoblastoma cell line HepG2, mRNA and protein levels of YAP1 were detected by real-time fluorescent quantitative PCR (RT-qPCR) and Western blot. And cellular proliferation and apoptosis were examined by CCK-8 assay and flow cytometry. Results The positive expression rate of YAP1 was 50.00%(19/38) in hepatoblastoma tissues and it was significantly higher than that in para-tumor tissues (0.00%, 0/21) (χ2=15.49, P<0.01). And its expression level was negatively correlated with patient prognosis. The positive expression rate of β-catenin protein was 52.63% (20/38) in hepatoblastoma tissues. However, there was no expression in para-tumor tissues. The expression level of YAP1 was positively correlated with that of β-catenin. After transfecting siRNA of YAP1, the expression of mRNA and protein of YAP1 were significantly lower in HepG2 cells than those in control group. Cell proliferating capacity decreased while apoptosis rate increased. Conclusions Highly expressed in pediatric hepatoblastoma cells, YAP1 is negatively correlated with patient prognosis. YAP1 and β-catenin may jointly promote the growth of hepatoblastoma. And YAP1 may be a new therapeutic target for pediatric hepatoblastoma. Key words: Hepatoblastoma; Beta catenin; Prognosis; Cell proliferation; Apoptosis; Yes-associated protein 1